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Dehydroabietylamine Ureas and Thioureas as Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Enhance the Antitumor Effect of Temozolomide on Glioblastoma Cells
journal contribution
posted on 2019-08-20, 16:03 authored by Kseniya Kovaleva, Olga Oleshko, Evgeniya Mamontova, Olga Yarovaya, Olga Zakharova, Alexandra Zakharenko, Alena Kononova, Nadezhda Dyrkheeva, Sergey Cheresiz, Andrey Pokrovsky, Olga Lavrik, Nariman SalakhutdinovA new class of tyrosyl-DNA phosphodiesterase
1 (TDP1) inhibitors
was found among resin acid derivatives. Several novel ureas and thioureas
derived from dehydroabietylamine were synthesized and tested for TDP1
inhibition. The synthesized compounds showed IC50 values
in the range of 0.1 to 3.7 μM and demonstrated low cytotoxicity
against the human tumor cell lines U-937, U-87MG, MDA-MB, SK-Mel8,
A-549, MCF7, T98G, and SNB19. Several compounds showed enhancement
of the cytotoxic activity of the alkylating agent temozolomide, which
is used as a first line therapy against glioblastoma (GBM), in the
GBM cell lines U-87MG and SNB19.
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Keywords
line therapySeveral novel ureasDehydroabietylamine UreasTyrosyl-DNA Phosphodiesterase 1 InhibitorsTDP 1 inhibitionGlioblastoma CellsAntitumor Effectalkylating agent temozolomidecytotoxic activityIC 50 valuesMDA-MB3.7 μ MSNB 19.compoundtyrosyl-DNA phosphodiesterase 1GBM cell lines U -87MGMCF98Gresin acid derivatives
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